title: A liquid chromatography-tandem mass spectrometry method for pharmacokinetics and tissue distribution of a camptothecin quaternary derivative in rats.
abstract: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to identify and quantify the camptothecin quaternary derivative CPT8 for application in pharmacokinetics and tissue distribution studies. Rat plasma and tissue samples were extracted with methanol by using camptothecin as the internal standard (IS). Chromatographic separation of CPT8 and the IS was achieved using a Hypersil GOLD C18 column, with a flow rate of 1.0 mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in the positive ion mode and by applying multiple reaction monitoring. The MS/MS ion transitions were monitored at m/z 484.3-361.2 for CPT8 and m/z 349.0-305.2 for the IS (CPT). A calibration curve was constructed using CPT8 concentrations ranging from 2.5 ng/mL to 2500 ng/mL (r>0.993). The efficiency of CPT8 extraction from plasma and tissue samples ranged from 91.23% to 105.4%. Intra- and inter-day precision (relative standard deviation) values were 0.21% and 7.25%, respectively. No matrix effects were observed. The freeze-thaw stability, post-extraction stability, and stability following short- and long-term storage at low temperatures ranged from 84.12% to 108.2%. The preclinical data obtained using this method is expected to facilitate future clinical investigations of CPT8.
authors.affiliation: The Key Laboratory of Forestry Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, China; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: li_qingyong@126.com.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Li
authors.forename: Qiaochu
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xueke
authors.initials: X
authors.lastname: Zhang
authors.forename: Changlong
authors.initials: C
authors.lastname: Hua
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Deng
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhao
authors.forename: Baihe
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D029769:Camptotheca / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D010936:Plant Extracts / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: D010936:Plant Extracts; D002166:Camptothecin
keywords: Camptothecin derivative; LC–MS/MS; Pharmacokinetics; Tissue distribution